I have almost completed my fellowship in gastroenterology and am using my new skills as a clinical investigator and molecule geneticist to solve problems in early diagnosis an pathogenesis of gastrointestinal cancer. i worked for six years in molecular biology medical school and have partially caught up with progress in medical genetics which occurred during medical school and my residency. I have been given the opportunity under supervision to independently pose hypotheses, to design experiments and to carry them out. I have found that working with ulcerative colitis patients at high risk for developing cancer is an excellent way to further my primary interest in reducing to clinical practice the discoveries of basic science. I have a strong desire to learn more about the pathogenesis of gastrointestinal cancer. The type of research done in this laboratory and the colleagues available to advise me are ideal ways to attain this goal. My primary sponsor is Dr. Rubin clinical investigator, gastroenterologist, and past mentor of many excellent academic gastroenterologists. My co- sponsors are Dr. Rodger Haggitt, an outstanding gastrointestinal pathologist and Dr. Sum Lee, a superb clinical investigator teacher. The laboratory facilities available to me are more than adequate and all of my sponsors have promised to help support my research despite the current difficult financial environment. The long term objective of our research group is to gain better understanding of the molecular mechanisms of neoplastic progression in the dysplasia and cancer associated with ulcerative colitis. In the process we hope to develop earlier and more cost effective methods of diagnosing curable cancer and it's precursors. We hope to do these studies in three ways: 1. To use molecular genetic techniques on colectomy specimens to study the pathogenesis of colon cancer. 2. To prospectively study biopsies taken during surveillance colonoscopy to find markers predictive of dysplasia. 3. To develop a screening blood test to target the UC patients at highest risk for developing dysplasia or cancer. I am currently managing the day to day operation of a molecular genetics laboratory with the assistance of Dr. Rabinovitch. With the support of this K08 I hope to complete my training in molecular genetics and to continue collaborative research.